The palladium-catalyzed reaction of aryl halides with terminal alkynes, known as the Sonogashira reaction, constitutes an important aspect of alkyne as well as of organopalladium chemistry.1,2 This reaction is generally co-catalyzed by Cu(I), and an amine as a base and a phosphine as a ligand for palladium are also typically included.3 An important side reaction encountered with the presence of a Cu(I) co-catalyst is the Glaser-type oxidative dimerization of the alkyne.4 To address this issue, several reports have described copper-free Sonogashira reactions, but none of them are free of an amine and a ligand simultaneously, while also operating at room temperature. For example, in 1986, Cacchi et al. reported the coupling of enol triflates with terminal alkynes under copper-free conditions, but a phosphine-ligated palladium precursor and a temperature of 60° C. was employed.5 In 1993, Linstrumelle published a paper on the Pd-catalyzed coupling of aryl or vinyl halides (I, Br, OTf) with terminal alkynes.6 In this report, only one example of a phosphine and copper-free (but not amine-free) Sonogashira coupling of a vinyl iodide with a terminal alkyne was described and the coupling proceeded in only moderate yield (57%). For an aryl iodide (only iodobenzene was used), a phosphine-ligated palladium source was included under copper-free conditions. In both cases, 5 mol % palladium catalyst was employed.
Herrmann reported a procedure for the Sonogashira reaction of aryl bromides, but it was necessary to use air-sensitive and pyrophoric P(t-Bu)3 as a ligand, although the coupling did proceed with only 0.5 mol % of palladium and ligand.7 It is worthy of mention that P(t-Bu)3 can be replaced with the air-stable [(t-Bu)3PH]BF4 in Sonogashira couplings.8 Ryu described a Sonogashira method for coupling aryl iodides in ionic liquids, but it required an elevated temperature (60° C.) as well as the use of a phosphine ligand.9 
Recently, Nájera has disclosed a palladacycle catalyst for the cross-coupling of aryl iodides and terminal alkynes.10 However, this methodology requires relatively harsh conditions (110° C.) and a multi-step synthesis of the catalyst, which is a benzophenone oxime. TBAF, TBAOH, and Ag2O were used by Mori as activators for the Sonogashira coupling of aryl iodides, but an elevated temperature (60° C.) and a phosphine-based palladium-catalyst were needed in all three cases.11 Moreover, use of a silver catalyst not only would add cost to the catalyst but also to the expense of metal waste disposal/recovery.
Astruc described the use of a preformed Pd(II)-phosphine catalyst for a Sonogashira coupling of aryl halides in neat Et3N.12 Leadbeater has reported a copper-free Sonogashira methodology for aryl iodides and activated aryl bromides with the traditional palladium catalyst Pd(PPh3)2Cl2 (4 mol %) at 70° C. in neat piperidine.13 Interestingly, however, the observation was made that under phosphine and copper-free conditions, neither palladium acetate nor palladium on charcoal catalyzed the aforementioned reaction. More recently, a report by Buchwald has appeared describing the coupling of aryl chlorides and aryl tosylates with terminal alkynes, utilizing a bulky biphenylphosphine ligand under copper and amine-free conditions.14 
Therefore, there is a continuing need for improved catalyst systems for Sonogashira coupling reactions.